Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m

Berger, Marc Moritz; Sareban, Mahdi; Schiefer, Lisa M.; Swenson, Kai E.; Treff, Franziska; Schäfer, Larissa; Schmidt, Peter; Schimke, Magdalena; Paar, Michael; Niebauer, Josef; Cogo, Annalisa; Kriemler, Susi; Schwery, Stefan; Pickerodt, Philipp A.; Mayer, Benjamin; Bärtsch, Peter; Swenson, Erik R.

doi:10.1152/japplphysiol.00806.2021

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…In contrast to our findings, B erger et al [ 48 ] found that acetazolamide did not lower PAP in healthy climbers who are susceptible to high-altitude pulmonary oedema; however, with a study size of 13 participants, a sufficient sample size according to their calculation could not be reached and therefore results should be interpreted with caution. Negative results were also reported in another study conducted in 15 healthy lowlanders travelling to the Bolivian Altiplano, in whom acetazolamide affected neither maximum exercise capacity nor pulmonary pressure/CO flow at rest and during exercise [ 49 ].…”

Section: Discussioncontrasting

confidence: 99%

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

et al. 2022

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BackgroundChronic obstructive pulmonary disease (COPD) may predispose to symptomatic pulmonary hypertension at high altitude. We investigated hemodynamic changes in lowlanders with COPD ascending to 3100m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP).MethodsIn this placebo-controlled, double-blind parallel-group trial, patients with COPD GOLD 2–3 living <800 m, SpO2>92%, PaCO2<6kPa, were randomized to receive either acetazolamide (125 0-250 mg d−1) or placebo capsules starting 24h before ascent from 760 m and during a 2-day-stay at 3100 m. Echocardiography, pulse-oximetry and clinical assessments were performed at 760m and after the first night at 3100m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG).Results112 patients, 68% men, mean±sdage 59±8 y, FEV161±12%pred, SpO295±2% were included. TRPG increased from 22±7 to 30±10 mmHg in 54 allocated to placebo and from 20±5 to 24±7 mmHg in 58 allocated to acetazolamide (both p<0.05) resulting in a mean (95%CI) treatment effect of −5 (−9 to −1)mmHg (p=0.015). In patients assigned to placebo at 760/3100m, SpO2was 95±2/88±3%, in the acetazolamide group respective values were 94±2/ 90±3% (both p<0.05) resulting in a treatment effect of +2(1 to 3)% (p= 0.001).ConclusionsIn lowlanders with COPD travelling to 3100m preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation.

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Section: Discussioncontrasting

confidence: 99%

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

et al. 2022

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“…A randomized, placebo-controlled, double-blind study of 13 healthy unacclimatized lowlanders with a history of HAPE found no significant reduction in the incidence of HAPE or pulmonary artery pressure after rapid ascent to 4559 m in those taking acetazolamide compared with placebo despite reductions in AMS and improved oxygenation. 121 Clinical observations suggest that acetazolamide may prevent re-entry HAPE, 122 a disorder seen in individuals who reside at high altitude, travel to lower elevation, and then develop HAPE upon rapid return to their residence.…”

Section: Preventionmentioning

confidence: 99%

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update

Luks,

Beidleman,

Freer

et al. 2023

Wilderness & Environmental Medicine

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To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

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“…In both studies, healthy, non-acclimatized individuals ascended within 20 h from 1,130 to 4,559 m (Capanna Regina Margherita), with an intervening overnight stay at 3,611 m (Gnifetti Hut). The designs and main outcomes of both studies have been published previously ( Berger et al, 2018 ; Berger et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…In study B, conducted in 2019, thirteen lowlanders with a previous history of radiographically documented HAPE were randomly assigned to acetazolamide (250 mg orally three times per day) or placebo. Medication started 2 days before ascent and continued until the end of the study ( Berger et al, 2022 ). Measurements were done at low altitude (baseline, 423 m) and 5, 19, 29, 43, 53, and 67 h after ascent to high altitude.…”

Section: Methodsmentioning

confidence: 99%

“…Assessment of right ventricular pressure gradient, high altitude pulmonary edema, and acute mountain sickness As described previously in detail (Berger et al, 2017;Berger et al, 2022) transthoracic echocardiography was performed to assess the right ventricular to atrial pressure gradient as a surrogate parameter for pulmonary artery pressure, and chest radiography for diagnosing HAPE. HAPH was defined as systolic pulmonary artery pressure >50 mmHg according to the definition by (León-Velarde et al, 2005).…”

Section: Study Participants and Protocolsmentioning

confidence: 99%

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Asymmetric and symmetric dimethylarginine in high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE)

Hannemann,

Freytag,

Schiefer

et al. 2023

Front. Physiol.

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Introduction: High altitude exposure may lead to high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE). The pathophysiologic processes of both entities have been linked to decreased nitric oxide (NO) availability.Methods: We studied the effect of acute high altitude exposure on the plasma concentrations of asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-arginine, L-ornithine, and L-citrulline in two independent studies. We further investigated whether these biomarkers involved in NO metabolism were related to HAPH and HAPE, respectively. Fifty (study A) and thirteen (study B) non-acclimatized lowlanders were exposed to 4,559 m for 44 and 67 h, respectively. In contrast to study A, the participants in study B were characterized by a history of at least one episode of HAPE. Arterial blood gases and biomarker concentrations in venous plasma were assessed at low altitude (baseline) and repeatedly at high altitude. HAPE was diagnosed by chest radiography, and HAPH by measuring right ventricular to atrial pressure gradient (RVPG) with transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and the AMS-C score.Results: In both studies SDMA concentration significantly increased at high altitude. ADMA baseline concentrations were higher in individuals with HAPE susceptibility (study B) compared to those without (study A). However, upon high altitude exposure ADMA only increased in individuals without HAPE susceptibility, while there was no further increase in those with HAPE susceptibility. We observed an acute and transient decrease of L-ornithine and a more delayed but prolonged reduction of L-citrulline during high altitude exposure. In both studies SDMA positively correlated and L-ornithine negatively correlated with RVPG. ADMA was significantly associated with the occurrence of HAPE (study B). ADMA and SDMA were inversely correlated with alveolar PO2, while L-ornithine was inversely correlated with blood oxygenation and haemoglobin levels, respectively.Discussion: In non-acclimatized individuals ADMA and SDMA, two biomarkers decreasing endothelial NO production, increased after acute exposure to 4,559 m. The observed biomarker changes suggest that both NO synthesis and arginase pathways are involved in the pathophysiology of HAPH and HAPE.

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Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m

Cited by 9 publications

References 45 publications

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update

Asymmetric and symmetric dimethylarginine in high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE)

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